Butyl lithium titration methods
1) The GILMAN Double Titration (J. Organomet. Chem. 1964, 2, 447 – 454.)
The most reliable method to determine the concentration of an organolithium is still
the double titration procedure described by Gilman 40 years ago. It is preferred over
single titration methods because it not only gives the concentration of the solution but
also provides an indication of the quality of the organolithium.
To determine the total content of base, an aliquot (usually 0.50 to 1.5 ml, depending
on the expected concentration) of the solution of the organolithium is quenched with
20 ml of water. The resulting solution of LiOH is titrated with a solution of
standardised hydrochloric acid using phenolphthalein as the indicator. To determine
the residual content of base of the organolithium, an aliquot (preferably the same
amount as before) of the organolithium is reacted with 1,2-dibromoethane as follows:
0.20 ml of dry 1,2-dibromoethane (BE CAREFUL: CARCENOGENIC) are dissolved
in 3 ml of dry DEE in an inert atmosphere. The organolithium is added dropwise with
vigorous stirring. After 5 min of stirring, the solution is diliuted with 20 ml of water
and then titrated as described above. 1,2-Dibromethane reacts with organolithiums as
follows:
R Li
Br
Br
R H
Br
LiBr
This procedure destroys the organolithium without producing LiOH, so that the
difference of the two titrations gives the exact concentration of the organolithium. A
typicale example is given below:
I. A 0.50 ml aliquot of a solution of n-BuLi in hexanes was quenched with water,
treated with a few drops of a phenolphthalein solution in water/methanol and titrated
with standardised hydrochloric acid unitil complete disappereance of the pink colour.
When titrating highly flammable organometallics such as t-BuLi, step I should be
carried out with degassed water under nitrogen.
II. A second 0.50 ml aliquot was quenchend with dibromoethane as described above.
After 5 min of stirring, the mixture was diluted with water and after addition of the
indicater titrated (with vigorous stirring – it is a biphasic system).
c(HCl) = 0.1034 N; V(HCl)I = 7.90 ml; V(HCl)II = 0.25 ml.
V(HCl)eff = V(HCl)I – V(HCl)II = 7.90 ml – 0.25 ml = 7.65 ml
c(n-BuLi) = [V(HCl)eff x c(HCl)] / V(aliquot) = [7.65 ml x 0.1034 mmol ml-1] / 0.50 ml
= 1.58 M
Residual base = [0.25 ml / 7.90 ml] x 100 % = 3.2 %. This value is typical for a high
quality organolithium. If the content of residual base is higher than ~ 10 % of the total
content of base, the quality of the organolithium is poor, which may be detrimental to
very sensitive reactions.
2) Single Titration Method
This titration method widely used and is perhaps more rapid than the Gilman method
described above, but has the disadvantage that it is a measure only of the total base
concentration. You may also find that it is difficult to see the end point of the titration
as you are looking for a colour change from dark yellow to orange-red. In order to
obtain an accurate titre, it is necessary to carry out the titration at least three times
and calculate an average of the results obtained.
Li
H
N
Ts
N
BuLi
H
N
Ts
N
Li
red-orange
1,3-diphenyl-2-propane p-toluenesulfonylhydrazide (approx. 200 mg) is placed into a
dry 10 mL, round-bottomed flask equipped with a magnetic stirrer bar and septum.
The system should then be purged with argon or nitrogen and kept under a positive
pressure of inert gas.
Dry THF is then added (4 mL) via syringe and the reaction mixture stirred rapidly to
dissolve the hydrazone. The butyl lithium solution should then be added dropwise
from an acurate 1 mL syringe until the yellow solution reaches the orange-red end
point. The volume of butyl lithium required should then be noted and the following
equation used to determine the molarity of the solution.
Molarity of BuLi = [(1000 x no moles hydrazone)/volume butyl lithium]
For a discussion of other titration methods see: J. Suffert, J. Org. Chem. 1989, 54,
509.